Wound recovery efficacy of retinol based-micellar formulations in an organotypic skin wound model.

Impairment of the skin's structural integrity initially results in acute wounds which can become chronic if timely wound closure is not achieved. Chronic wounds (CWs) affect more than 1% of the global population with increasing cases of this condition due to the ageing population. Current wound management relies on debridement, hyperbaric oxygen, antibiotics, and wound dressings, which lack early intervention and specificity. Herein, antibiotics-free retinol-based micellar formulations (RMF) were made and their wound healing efficacy were investigated in vitro. Five different formulations with retinol contents of 0.3% and 1% against a placebo were topically applied to an organotypic full-thickness skin wound model (FT-SWM, MatTek®) with a 3 mm punch wound, and maintained in an incubator for 6 days. The histological analysis of the FT-SWM was conducted at depths of 60 µm and 80 µm. It was found that all the micellar retinol formulations accelerated wound bed contraction, with 0.3% RMF demonstrating the highest efficacy. At the depths of 60 µm and 80 µm, the 0.3% RMF exhibited inner wound diameter contraction of 58% and 77%, respectively, in comparison to the placebo showing 15% and 8%. The RMF significantly accelerated wound healing and can thus be a potential early intervention for speedy wound recovery. It should be pointed out that these results were obtained based on a small sample size and a large sample size will be explored to further validate the results.

Non-Antibiotic Compounds Synergistically Kill Chronic Wound-Associated Bacteria and Disrupt Their Biofilms.

Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent development of biofilms within the wound area necessitates the identification of novel treatment strategies for use within infected chronic wounds. Here, several non-antibiotic compounds, polyhexamethylene biguanide (PHMB), curcumin, retinol, polysorbate 40, ethanol, and D-α-tocopheryl polyethylene glycol succinate 1000 (TPGS) were screened for their antibacterial and antibiofilm capabilities. The minimum inhibitory concentration (MIC) and crystal violet (CV) biofilm clearance against two bacteria frequently associated with infected chronic wounds, Staphylococcus aureus and Pseudomonas aeruginosa, were determined. PHMB was observed to have highly effective antibacterial activity against both bacteria, but its ability to disperse biofilms at MIC levels was variable. Meanwhile, TPGS had limited inhibitory activity but demonstrated potent antibiofilm properties. The subsequent combination of these two compounds in a formulation resulted in a synergistic enhancement of their capability to kill both S. aureus and P. aeruginosa and disperse their biofilms. Collectively, this work highlights the utility of combinatory approaches to the treatment of infected chronic wounds where bacterial colonization and biofilm formation remains significant issues.

Antibiotics-Free Compounds for Chronic Wound Healing.

The rapid rise in the health burden associated with chronic wounds is of great concern to policymakers, academia, and industry. This could be attributed to the devastating implications of this condition, and specifically, chronic wounds which have been linked to invasive microbial infections affecting patients' quality of life. Unfortunately, antibiotics are not always helpful due to their poor penetration of bacterial biofilms and the emergence of antimicrobial resistance. Hence, there is an urgent need to explore antibiotics-free compounds/formulations with proven or potential antimicrobial, anti-inflammatory, antioxidant, and wound healing efficacy. The mechanism of antibiotics-free compounds is thought to include the disruption of the bacteria cell structure, preventing cell division, membrane porins, motility, and the formation of a biofilm. Furthermore, some of these compounds foster tissue regeneration by modulating growth factor expression. In this review article, the focus is placed on a number of non-antibiotic compounds possessing some of the aforementioned pharmacological and physiological activities. Specific interest is given to Aloevera, curcumin, cinnamaldehyde, polyhexanide, retinoids, ascorbate, tocochromanols, and chitosan. These compounds (when alone or in formulation with other biologically active molecules) could be a dependable alternative in the management or prevention of chronic wounds.

Microwave plasma rapid heating towards robust cathode/electrolyte interface for solid oxide fuel cells.

Mixed electronic and ionic conductivity (MIEC) perovskite oxides hold promise as cathode with high oxygen reduction reaction (ORR) activity for solid oxide fuel cells (SOFCs) operating at reduced temperatures. However, these MIEC cathodes usually contain lanthanide or alkaline-earth elements at A-site. These elements tend to interact with yttria-stabilized zirconia electrolyte (YSZ) to form unwanted phases such as La2Zr2O7 and SrZrO3 at conventional electrode fabrication conditions (>800 °C). Such unwanted interfacial reaction severely degrades the cell performance. We present a new method to assemble SrCo0.4Fe0.5W0.1O3-δ (SCFW) directly onto YSZ by a highly efficient microwave plasma technique. Intimate contact between SCFW and YSZ phases can be achieved by ten-minute microwave-plasma treatment with no new phase formation. Consequently, the microwave-plasma fabricated interface exhibits a notably high ORR performance, showing an area-specific resistances of 0.11 Ω cm2 at 600 °C, about two orders of magnitude better than the equivalent prepared via the conventional method. Our method is also effective in assembling other MIEC perovskite cathodes such as SrCo0.5Fe0.5O3-δ and SrCo0.8Nb0.1Ta0.1O3-δ on YSZ electrolyte, achieving notable enhancement of the cathode performance. This study thus provides an effective and convenient method for synthesizing reactive and robust interfaces between two incompatible phases with minimized interphase interactions.

Impact breakage of single pharmaceutical tablets in an air gun.

Milling is commonly used for controlling the size distribution of granules in the pharmaceutical dry granulation process. A thorough understanding of the breakage of single compacts is crucial in unravelling the complex interactions that exist between different pharmaceutical feed materials and the mill process conditions. However, limited studies in the literature have examined the impact breakage of single pharmaceutical compacts. In this study, pharmaceutical powders including the microcrystalline MCC 101, MCC 102 and MCC DG were compressed at different pressures and tablets with different porosities and thicknesses were produced. Impact breakage tests were conducted in an air gun and the tablet impact velocities and breakage patterns were analysed using a Phantom ultrahigh-speed camera. It was observed that the tablet breakage rate and the amount of fines reduced as the tablet porosity decreased. In addition, thin tablets with low porosity exhibited semi-brittle fracture and less intense crack propagation while thick tablets with high porosity primarily disintegrated into fine fragments. Thus, this study provides a better understanding of the breakage behaviour of different pharmaceutical materials and can potentially be used to describe the breakage modes of compacts in the ribbon milling processes.

The effects of screw-to-roll speed ratio on ribbon porosity during roll compaction.

Dry granulation through roll compaction is a technology commonly used in the pharmaceutical industry for producing roll compacted ribbons. The significance of the feed screw speed and roll speed during ribbon production was highlighted in recent publications. However, previous studies focused primarily on the individual effects of either the feed screw speed or roll speed on ribbon porosity, and the synergetic effect of these parameters was rarely examined. The aim of this study therefore was to investigate the effects of the screw-to-roll speed ratio on the porosity of roll compacted ribbons, produced at different roll compaction conditions using the microcrystalline cellulose MCC, Avicel PH-102 feed material. It was observed that ribbon porosity decreased linearly with increasing screw-to-roll speed ratio. Furthermore, an increase in the speed ratio led to an increase in the roll gap and mass throughput while a decrease in the screw constant was observed. Thus, this study demonstrates that the screw-to-roll speed ratio can be treated as one of the critical process parameters for controlling ribbon porosity and can also be used to determine the optimum operating regimes during roll compaction.

Impact of feed material properties on the milling of pharmaceutical ribbons: A PBM analysis.

Dry granulation is commonly used in the pharmaceutical industry for compressing heat and moisture sensitive feed materials into compacts, subsequently followed by milling. Population balance models (PBMs) are often used to explore the effects of milling conditions on the granule size distribution (GSD) but limited studies have investigated the effects of the feed material and ribbon properties on the resulting GSD. In this work, a variety of feed materials and ribbons with different mechanical properties were used to validate a mass-based bi-modal breakage function developed in a previous study (Olaleye et al., 2019). Ribbon like tablets (referred to as ribblets) with a range of precisely controlled porosities were produced using an Instron machine and pharmaceutical excipients including the microcrystalline cellulose MCC 101, MCC DG and a DCPA/MCC mixture. Roll compacted ribbons were also produced using MCC 102 and MCC DG excipients. The ribblets and ribbons were milled in an impact-dominated cutting mill and PBM parameters were obtained from the ribblet milling data. Mechanistic models related to the feed ribbon property were then developed. It was found that the PBM with the mass-based bi-modal breakage function can accurately predict the GSDs of both the milled ribblets and roll compacted ribbons. The model developed was successfully linked to ribbon properties such as porosity for the first time and the model parameter a that reflects the fines mode in the bi-modal breakage function increased linearly with ribblet porosity. This work demonstrates the versatility of the developed PBM and provides a systematic approach for describing the ribbon milling process.

Population balance modelling of ribbon milling with a new mass-based breakage function.

Dry granulation through roll compaction followed by milling is a widely used pharmaceutical process. The material properties of powders and the roll compaction process conditions affect the strength of ribbons, and subsequently the granule size distribution (GSD). Accurate prediction of the granule size distribution from milling of ribbons with different properties is essential for ensuring tablet quality in the final compaction stage. In this study, MCC, PH-102 ribbons with precisely controlled porosities were produced and milled in a cutting mill and granule size distribution was analysed using QicPic. A population balance model with a new breakage function based on the Weibull function was developed to model the ribbon milling process. Eight model parameters were initially obtained for each ribbon porosity and very good agreement between the model and experimental results was obtained. Sensitivity analysis was then performed and thus reduced the number of model parameters that changed with ribbon porosity to two in the breakage function. The refined model was able to predict the granule size distribution both within and outside the experimental boundaries. It was shown that the model developed in this study has a great potential for predicting granule properties and therefore the optimisation of the dry granulation process.

Strontium-doped lanthanum iron nickelate oxide as highly efficient electrocatalysts for oxygen evolution reaction.

Pursuing efficient and low-cost catalysts for the sluggish oxygen evolution reaction (OER) is imperative for the large-scale deployment of promising electrochemical technologies such as water splitting and CO2 electrochemical reduction. The earth-abundant perovskite catalysts based on LaNiO3-δ show promise in OER catalysis because of their relatively low cost and their optimal electronic structure but suffer from low electrode-area normalized activity. In this work, we partially substituted La with Sr and Ni with Fe to enable a remarkably high OER activity with an ultra-low overpotential of 374 ±â€¯3 mV vs RHE at a current density of 10 mA cm-2 normalized by electrode geometric area. This performance even surpasses the performance of benchmark RuO2. Our results show that Sr could promote OER-active sites including Ni(III), O2-2/O-, and optimal Ni/Fe ratios, which significantly improve the surface intrinsic activity at the perovskite surface. Therefore, this work not only developed a highly efficient earth-abundant catalyst towards OER, but also demonstrated the effective modulation of catalyst surface interactions through A-site doping for perovskite oxides for key applications such as water splitting, CO2 electrochemical reduction and N2 electrochemical fixations.